A randomized trial of amantadine in Huntington disease

Context: Huntington chorea, like levodopa-induced dyskinesias, may be responsive to amantadine hydrochloride treatment. Objectives: To measure the effect of amantadine treatment on Huntington chorea and to test a hypothesis that the adventitious movements are associated with reduced central proprioception that can be corrected by amantadine treatment. Design: A randomized placebo-controlled cross-over trial with 2 weeks of treatment. Setting: A tertiary referral center. Participants: Twenty-four subjects with Huntington disease took amantadine hydrochloride, 100 mg 3 times daily for 2 weeks, and placebo for 2 weeks. Methods: Chorea of the face, trunk, and limbs while seated was videotaped at baseline and after each study phase. Segments were viewed in random order by blinded reviewers and scored. Proprioception was determined using arm restraints in which the right and left elbows were set at slightly different angles, and the errors in selecting the more extended elbow over 40 trials were recorded. Results: The chorea score was not correlated with a proprioception deficit. Neither chorea nor proprioception were significantly affected by amantadine therapy. The chorea score was 9.6 (3.1) points at baseline and 9.7 (3.7) points when the patient was receiving amantadine therapy. The 95% confidence interval for the difference between placebo effect and amantadine effect was -1.43 to 1.0 points. Despite this, 19 subjects felt improved during the amantadine phase compared with 6 subjects improved in the placebo phase (P=.006) and the quality of life was better (P<.001). Conclusions: Elbow proprioception was not shown to be related to Huntington chorea. Amantadine hydrochloride treatment at doses of 300 mg/d had no effect, on average, for Huntington chorea, although most patients felt subjectively better during the short course of amantadine treatment.